Traumatic brain injury (TBI) is associated with long-term deficit in cognitive abilities and elevated risk for psychiatric disorders. The pathology of TBI is very complex involving multiple cascades of molecular and cellular events, which are difficult to target with pharmacological therapies that are too confined. An overlooked aspect of TBI is damage to plasma membranes, which may reduce neuronal excitability and interneuronal signaling, thereby affecting fundamental mechanisms required for processing and storage of information. In turn, the dysfunction in energy management resulting from TBI imposes a heavy toll on the multitude of neuronal processes that rely on energy, and can affect membrane structure and function. Abundant evidence in the human literature emphasizes the importance of dietary omega-3 fatty acids to reduce the incidence of psychiatric disorders. According to our studies, the benevolent action of DHA on rodent TBI seems related to supporting membrane stability. In turn, the curry spice curcumin, traditionally known in Asia for its medicinal power, has been shown in our hands to promote energy homeostasis and reduce the learning impairment after TBI. In addition, our new preliminary data point out the capacities of DHA and curcumin to attenuate anxiety- like behaviors. Although exercise is an excellent therapy to promote cognitive and emotional enhancement across several conditions and ages, its deployment after TBI requires optimization. Our strategy involves the use of the intrinsic capacity of the omega-3 fatty acid DHA to support plasma membranes, and the power of curcumin to support energy metabolism. We expect that this dietary therapy can contribute to the effects of exercise after TBI, and can have long-term consequences for mechanisms responsible for maintaining higher order operations such as learning and memory, and emotions. We will use a rodent model of concussion injury to evaluate crucial mechanisms that can restore membrane function, and assess their effects on reducing anxiety-like behaviors and cognition. Our comprehensive approach based on noninvasive interventions to promote neuronal stability and mental health after TBI has an outstanding safety profile, and information derived from these studies can be readily translatable into human treatments. PUBLIC HEALTH RELEVANCE: We will pursue studies to understand how dietary factors can complement the action of exercise to reduce the consequences of TBI. TBI disrupts molecular systems that maintain membrane function and synaptic plasticity. Our design relies on the powerful action of select dietary factors and exercise to modulate membrane physiology, synaptic function, and to enhance cognitive abilities.